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Article

Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study

1
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
2
Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima 734-8551, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Jeffrey Lipman
Antibiotics 2022, 11(7), 982; https://doi.org/10.3390/antibiotics11070982
Received: 28 June 2022 / Revised: 15 July 2022 / Accepted: 19 July 2022 / Published: 21 July 2022
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
The bacterium Pseudomonas aeruginosa is known to be associated with nosocomial infections around the world. Pazufloxacin, a potent DNA gyrase inhibitor, is known to be an effective drug candidate. However, it has not been clarified whether the pharmacokinetic (PK)/pharmacodynamic (PD) of pazufloxacin was effective against P. aeruginosa. Herein, we demonstrated that the PK/PD index of pazufloxacin against P. aeruginosa infection is used to optimize the dosing regiments. We constructed an in vivo infection model by infecting P. aeruginosa into the thigh of a mouse to determine the PD, and we measured the serum concentration of pazufloxacin to construct the PK model using high-performance liquid chromatography. The therapeutic efficacy of pazufloxacin was correlated with the ratio of the area under the free concentration time curve at 24 h to the minimum inhibitory concentration (fAUC24/MIC), and the maximum free concentration to the MIC (fCmax/MIC). Each contribution rate (R2) was 0.72 and 0.65, respectively, whereas the time at which the free drug concentration remained above the MIC (R2 = 0.28). The target value of pazufloxacin fAUC24/MIC for stasis was 46.1, for 1 log10 it was 63.8, and for 2 log10 it was 100.8. Moreover, fCmax/MIC for stasis was 5.5, for 1 log10 it was 7.1, and for 2 log10 it was 10.8. We demonstrated that the in vivo concentration-dependent activity of pazufloxacin was effective against the P. aeruginosa infection, and successfully made the PK/PD model sufficiently bactericidal. The PK/PD model will be beneficial in preventing the spread of nosocomial infections. View Full-Text
Keywords: pharmacokinetics; pharmacodynamics; pazufloxacin; Pseudomonas aeruginosa; murine thigh infection model pharmacokinetics; pharmacodynamics; pazufloxacin; Pseudomonas aeruginosa; murine thigh infection model
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MDPI and ACS Style

Umezaki, Y.; Matsumoto, K.; Ikawa, K.; Yokoyama, Y.; Enoki, Y.; Shigemi, A.; Watanabe, E.; Nakamura, K.; Ueno, K.; Terazono, H.; Morikawa, N.; Takeda, Y. Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study. Antibiotics 2022, 11, 982. https://doi.org/10.3390/antibiotics11070982

AMA Style

Umezaki Y, Matsumoto K, Ikawa K, Yokoyama Y, Enoki Y, Shigemi A, Watanabe E, Nakamura K, Ueno K, Terazono H, Morikawa N, Takeda Y. Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study. Antibiotics. 2022; 11(7):982. https://doi.org/10.3390/antibiotics11070982

Chicago/Turabian Style

Umezaki, Yasuhiro, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Yuki Enoki, Akari Shigemi, Erika Watanabe, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa, and Yasuo Takeda. 2022. "Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study" Antibiotics 11, no. 7: 982. https://doi.org/10.3390/antibiotics11070982

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